L7 - Virus uncoating Flashcards
What is the role of the ubiquitin ligase system in the cell?
It conjugates the small peptide ubiquitin (76 amino acids) to target proteins, marking them for degradation by the proteasome.
How do microtubules contribute to intracellular movement?
They serve as polarised highways where the dynamic + end is used for polymerisation/depolymerisation, while the – end is anchored at the microtubule organising centre (MTOC).
Which motor proteins facilitate movement along microtubules, and in what directions do they travel?
Kinesin moves cargo away from the MTOC, and dynein (with dynactin) moves cargo towards the MTOC.
What function do nuclear pore complexes (NPCs) serve in the cell?
NPCs act as gatekeepers for the nucleus, allowing passive diffusion for small proteins and mediating active transport for larger molecules via import and export factors.
What type of genome does adenovirus have, and where does its replication occur?
Adenovirus possesses a non-enveloped, linear double-stranded DNA genome of about 36,000 bp, and it replicates in the nucleus.
Which major structural proteins form the adenovirus capsid?
The capsid is mainly composed of hexon and penton base proteins, supported by several cement proteins.
Why is adenovirus often used in gene therapy and vaccine delivery?
Due to its well-characterised nature, ability to deliver genetic material, and established use as an anti-cancer agent and vaccine vector.
What is the significance of adenovirus being assembled as a “precursor” virus?
The precursor virus is formed in the nucleus and requires processing by a virally coded protease (AVP) to uncoat properly upon entry into a new cell.
How does adenovirus enter the host cell after attachment?
It is internalised via clathrin-mediated endocytosis into an endosome.
What triggers the initial disassembly of adenovirus within the endosome?
The drop in pH during endosome trafficking initiates partial degradation of the virus, leading to the release of mature protein VI.
What role does protein VI play in adenovirus uncoating?
Protein VI induces negative curvature in the endosomal membrane, lysing it to allow the virus to escape into the cytoplasm.
Why is the ubiquitination of protein VI important?
Ubiquitination of protein VI after endosomal escape is required to facilitate microtubule-mediated transport of the partially degraded virus.
How is the partially degraded adenovirus transported within the cell after endosomal escape?
It associates with microtubules via kinesin (attaching to the penton base) and dynein (attaching to the hexon), allowing it to ‘surf’ towards the nuclear pore complex.
What occurs when adenovirus reaches the nuclear pore complex (NPC)?
The virus docks with components Nup214 and Nup358, and ubiquitin ligases and the proteasome are recruited to further dismantle the capsid.
Which host ubiquitinase is involved at the NPC, and what does it do?
The ubiquitinase MIB1 triggers degradation of viral protein V, which is necessary for releasing the viral genome.
How does viral protein V contribute to genome release?
Protein V appears to affect the mechanical properties of the degrading virus particle, reversing the genome condensing effect of protein VII and aiding its import into the nucleus.
What structural forms can influenza particles take, and how is the viral genome organised?
Influenza particles can be round or filamentous; the genome segments are clustered at one end, associated with the matrix protein M1.
Describe the initial entry process of influenza virus into the host cell.
Influenza enters via micropinocytosis or endocytosis, with trafficking along microtubules or actin filaments; as the endosome matures, its pH drops.
What role does the M2 protein play during influenza uncoating?
M2 allows hydrogen ions to enter the viral particle, leading to the dissociation of M1 from the viral ribonucleoproteins.
How does the host cell contribute to influenza virus uncoating after endosomal fusion?
Exposure of unanchored ubiquitin chains upon fusion recruits HDAC6, which, along with molecular motors and aggresome components, exerts a shearing force to disassemble the viral interior.
What is the role of E3 ubiquitin ligase Itch in influenza uncoating?
It polyubiquitinates matrix protein M1, contributing to the uncoating process.
How does TNPO1 (transportin 1) assist influenza virus uncoating?
TNPO1 associates with M1 proteins, promoting their dissociation from the viral genome complexes.
What role do importins play after influenza uncoating?
Importins alpha and beta bind to the newly released viral ribonucleoproteins, facilitating their transport into the nucleus via the NPC.
How do adenovirus and influenza virus uncoating processes compare?
Both viruses utilise host cell functions, particularly the ubiquitin system, and rely on microtubule-mediated transport and NPC interaction to deliver their genomes to the nucleus.
What common host system is exploited by both adenovirus and influenza during uncoating?
Both viruses utilise components of the ubiquitin ligase system to tag viral proteins for degradation, which is critical for genome release.
What makes virus uncoating a complex process?
It involves multiple coordinated steps—including capsid disassembly, membrane disruption, intracellular transport, and nuclear import—each relying on distinct host factors and viral proteins.
Why is understanding virus uncoating important for virology?
It reveals potential targets for antiviral strategies and improves our overall understanding of virus–host interactions during the early stages of infection.
